Medical, chemical and biological laboratories utilize large volumes of microplates and related labware in their drug development and analytical programs, whether for the analysis of chemical or biological samples. To be cost effective, for tracking accuracy, and for reasons of health and safety, most modern high throughput laboratory analysis systems are automated, with extensive use being made of conveyors, robots, and other microplate handling devices integrated into the system to provide for rapid mechanical movement of the microplates in seriatim through a sequence of workstations, such workstations including, without limitation, plate de-lidders, plate readers, plate flippers, plate shakers, thermocylers and protein crystallography workstations. At each workstation, a pre-determined operation is performed on the respective sample contained in each microplate. Increasingly, such automated systems are under the centralized control of a personal computer (“PC”) or other CPU means programmed with commercially available control system software designed for this purpose. Each microplate is typically bar-coded or otherwise machine readably marked to allow for the individual identification and tracking of samples throughout the system. Some prior art control system software programs allows for customized processing of identified sub-sets of microplates of a larger run of microplates at one or more of the workstations. Moreover, some of these programs also allows for the accumulation, storage and analysis of statistical data pertaining to the processed samples.
Progressively, such prior art laboratory analysis systems have also become more modular in nature, thus allowing for the number, type and sequence of workstations to be re-organized and re-configured without the need for extensive re-design of the system hardware or software from scratch. This modularization has been facilitated by several factors, including, without limitation, the standardization of microplates and related labware to published industry standards, the increasing availability of standardized processing hardware (e.g. plate movers and workstations) having standardized electrical interfaces for easy connection to PC's, and the availability of increasingly versatile and user friendly control system software to run on such PC's.
More recently, in order to conserve valuable laboratory floor space, such high volume automated laboratory analysis systems have moved from strictly linear layouts, such as utilized in, for example, the CRS Model HSDM 40 MBS system available from Thermo Electron Corporation, of Burlington, Ontario, Canada, wherein a series of 40 thermocylers is laid out 20 on each side of a linear microplate transport axis defined by a conveyor belt based plate mover, to systems having a more dense three-dimensional layout, such as utilized, for example, in the CRS Model VAL 40 MBS system also available from Thermo Electron Corporation, of Burlington, Ontario, Canada, wherein 40 thermocylers are arranged in a semi-circular outline of 8 vertical banks, each bank having 5 thermocycler units stacked one above the other, with the 8 banks surrounding a robot having a SCARA arm which is able to grip a microplate and rapidly and accurately move it from a defined pick-up location to any one of the 40 thermocycler units and to subsequently retrieve the microplate from that thermocycler unit for return to its original location, or to another location within its reach, for subsequent processing by the automated analysis system.
Such advances in the prior art have not only reduced the space requirements for high throughput automated laboratory analysis systems, but have also significantly reduced the lost motion and long transport times associated with prior art systems laid out on a two-dimensional linear geometry. As such, the processing bottleneck in high throughput automated laboratory screening and analysis systems utilizing microplates has shifted from delivery and retrieval of the microplates to and from the workstations of the system to delivery of the microplates from storage into the automated system. This is so as known automated processing systems, such as those discussed above, typically have a storage facility of limited capacity connected directly to the system from which it can draw microplates for automated processing. An on-line storage facility of this type typically comprises a carousel having from six to eight removable “nests” (or “hotels”) each accommodating the storage of from about 20 to about 30 microplates. These nests are typically releasably hung around the outer circumference of the carousel frame for automated feeding into the laboratory analysis system by robots or other plate moving means. An example of such a carousel, with fixed nests, can be seen in U.S. patent applications Ser. No. 10/735,866 (Hass) published under Publication No. US 2004/0175258 on Sep. 9, 2004. An example of such a carousel, with removable nests, is the CRS Microplate Carousel available from Thermo Electron Corporation, of Burlington, Ontario, Canada. Not only are such prior art carousel storage devices unduly heavy and complex, due in part to the separate mounting hardware typically used to provide for such releasable mounting of the nests, but they must additionally provide plate locators on the nests to positively locate the microplates relative to the nests for accurate robotic gripping. Additionally, and more importantly, such on-line storage facilities must be continually replenished from a larger, standalone storage facility that is off-line (e.g. a larger refrigerated housing or heated incubator) typically containing many hundreds, if not thousands of microplates. This task is, in the prior art, typically carried out manually by laboratory personnel who restock the empty nests of the on-line storage facility with microplates retrieved from the off-line storage facility. Such work is not only tedious and time consuming, but keeps laboratory personnel from doing higher level tasks. Moreover, failure to timely replenish the on-line storage facility from the off-line storage facility may result in costly shut-downs of the automated system due to lack of microplates for processing.
It should also be considered that microplates manually loaded into the on-line storage facility for subsequent processing by the automated system are more likely to be subject to sequencing errors (i.e., being mixed up in their order) than machine identified and loaded microplates. Such sequencing errors can result in the samples contained within the microplates being improperly processed at the workstations of the system, as the position of each respective microplate within the system is based on the assumption that laboratory personnel initially set-up the on-line storage facility according to the worklist provided. Thus, such sequencing errors of the microplates can have potentially dire consequences. Additionally, manual movement of the microplates from the off-line storage facility and loading thereof into the on-line storage facility is subject to mishap (e.g., dropping of the microplates), with resultant loss of the samples contained within the microplates.
The above problems with prior art microplate storage facilities are compounded where the storage must be environmentally controlled, i.e., maintained at a temperature that is not ambient to the processing system. For example, it is known to store microplates for subsequent automated processing at temperatures that vary between about 95° Celsius to about minus 80° Celsius with varying controlled levels of humidity and CO2. In such cases, prior art environmentally controlled storage devices are severely limited for several additional reasons. With respect to environmentally controlled on-line microplate storage facilities, a well-known line of such devices is the Cytomat 6000 Series of automated incubators, available from Thermo Electron Corporation of Burlington, Ontario, Canada, which devices have a conventional storage carousel centrally positioned inside of a bulky, cuboidal incubated housing enclosure. Such large and bulky cuboidal housing enclosures prevent the nesting of these types of devices in sufficiently close proximity to one another to allow for efficient multiple placement around a centralized external microplate mover or robot, particularly where a circular or semi-circular array of the subject devices is desired to minimize the floorprint of the system. Moreover, the housing enclosure of such prior art environmentally controlled microplate storage devices have a single robotic arm positioned within the incubated housing enclosure, which robotic arm is limited in its operation to accessing only microplates stored in the carousel nest positioned immediately adjacent to the arm for delivery of such microplates to an area located immediately outside of a small door positioned in a front wall of the housing enclosure. These structural arrangements significantly limit the available options for efficiently incorporating prior art types of environmentally controlled on-line laboratory storage facilities into high throughput automated microplate analysis systems. Further, the placement of the robotic arm and its related equipment inside of an environmentally controlled housing enclosure introduces an extra heat load thereon and causes the robotic arm to operate in conditions of heat, cold, or humidity that may not be optimal to its performance, reliability or longevity. Moreover, such an extra heat load may cause temperature variations in the microplates positioned in proximity to the robotics. Such local temperature variations can cause undesirable effects on the sample characteristics, thus producing an uncontrolled basis of experimentation.
With respect to larger scale environmentally controlled off-line storage facilities, such as walk-up or walk-in refrigerators or incubators, the capacity of these units has to be planned for well in advance of their date of first use, and may often require facility restructuring, particularly in relation to any upsizing subsequent to initial facility construction. Moreover, the capital costs associated with such off-line bulk microplate storage facilities are significant, further limiting their availability.
Thus, there remains a need in the prior art for an improved environmentally controllable storage system suitable for use with microplates. This need is acute in relation to environmentally controllable storage systems for microplates that: (i) are suitable for on-line integration with other automated laboratory analysis equipment; (ii) are scalable to the desired throughput requirements of a user on an ongoing basis over time; (iii) eliminate or substantially reduce the need for large, off-line storage facilities; and (iv) provides for automated testing and analysis purposes an interim, or remote, large scale, mobile, on-line storage capability which obviates the need for restocking of frequently used test samples contained in microplates.
It is thus an object of the present invention to obviate or mitigate at least one of the above mentioned disadvantages associated with prior art storage devices.